The effects of tizanidine were studied in patients with spastic paresis. The study consisted of 4 parts: I, double-blind cross-over trial at maximal dosage 10 mg/day in 13 patients; II, open trial at maximal dosage 32 mg/day in 10 patients; III, long-term medication at dosage 32 mg/day for 6-15 months in 4 patients; IV, single dose (12 mg) administration in 3 patients. The effects were evaluated from clinical examinations, subjective assessments, EMG, gait analysis and quantitative determinations of passive resistance and voluntary strength in isokinetic extensions and flexions of the knee and plantar and dorsal flexions of the ankle at different speeds of motion. At 3-10 mg/day, no effects were observed except for increased prime mover EMG activity in voluntary knee flexions. At 12-32 mg/day, passive resistance decreased significantly in 3 of the movements tested. The maximal voluntary strength increased significantly in 3 movements, frequently associated with enlarged activation of prime mover muscles, less frequently with reduced antagonist co-activation. Functional disability was subjectively reduced and verified by improved gait capacity in 4 patients. Sustained effects on motor performance during long-term medication were verified by withdrawal in 3 patients. Single dose administration resulted in reduced passive resistance and increased voluntary strength, associated with an increased activation of the prime mover muscles. The results indicate that tizanidine exerts its effects in part by reducing spastic restraint, in part by enhancing the capacity to activate paretic muscles.